Abstract
The extracellular environment regulates the dynamic behaviors of cells. However, the effects of hydrostatic pressure (HP) on cell fate determination of mesenchymal stem cells (MSCs) are not clearly understood. Here, we established a cell culture chamber to control HP. Using this system, we found that the promotion of osteogenic differentiation by HP is depend on bone morphogenetic protein 2 (BMP2) expression regulated by Piezo type mechanosensitive ion channel component 1 (PIEZO1) in MSCs. The PIEZO1 was expressed and induced after HP loading in primary MSCs and MSC lines, UE7T-13 and SDP11. HP and Yoda1, an activator of PIEZO1, promoted BMP2 expression and osteoblast differentiation, whereas inhibits adipocyte differentiation. Conversely, PIEZO1 inhibition reduced osteoblast differentiation and BMP2 expression. Furthermore, Blocking of BMP2 function by noggin inhibits HP induced osteogenic maker genes expression. In addition, in an in vivo model of medaka with HP loading, HP promoted caudal fin ray development whereas inhibition of piezo1 using GsMTx4 suppressed its development. Thus, our results suggested that PIEZO1 is responsible for HP and could functions as a factor for cell fate determination of MSCs by regulating BMP2 expression.
Highlights
Osteoblast lineage cells and marrow adipocytes originate from a common progenitor cells in the bone marrow-derived mesenchymal stem cells (BMSCs)
To carry out cell culture under continuous hydrostatic pressure (HP) loading with our chamber, the cells should be cultured without medium change
Piezo type mechanosensitive ion channel component 1 (PIEZO1), but not PIEZO2 or TRPV4, was induced after 0.01 MPa HP loading (Figs 2e and 3e). These results suggest that the promotion of osteoblastic differentiation from MSCs by HP loading was correlated with PIEZO1 expression
Summary
Osteoblast lineage cells and marrow adipocytes originate from a common progenitor cells in the bone marrow-derived mesenchymal stem cells (BMSCs). Osteoblastogenesis and bone formation are mediated by several cytokines, including bone morphogenetic proteins (BMP), transforming growth factor β, Wnt, and hedgehog[11,12,13,14,15]. Among these factors, BMP2 is a potent growth factors that plays a critical role in osteoblast differentiation of MSCs and osteoprogenitor cells in vitro and in vivo[11,15]. During the process of osteogenesis from MSCs, two master transcription factors, RUNX2 ( termed CBFA1) and Osterix (OSX) are required for osteoblast differentiation[17,18]. The expression and function of mechanosensitive PIEZO ion channels in MSCs and osteoblasts have not yet been established
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